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      Tuesday, March 28, 2023
      News & Perspective Drugs & Diseases CME & Education Academy Video Decision Point
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      CME/CE Test

      Impact of Diagnostic Genetics on Remission MRD and Transplantation Outcomes in Older Patients With AML

      1. You are considering treatment options for your 70-year-old patient with acute myeloid leukemia (AML). According to the analysis by Murdock and colleagues, which of the following statements about baseline clinical and genetic determinants of posttransplant leukemia-free survival (LFS) in older patients with AML is correct?
        DDX41 and DNMT3A mutations present at diagnosis have unfavorable associations with LFS
        TP53 and JAK2 mutations present at diagnosis have favorable associations with LFS
        Baseline molecular risk, karyotype, hematopoietic cell transplantation comorbidity index (HCT-CI) score, complete response with incomplete blood recovery (CRi), and clinically defined secondary AML all have independent associations with LFS in a multivariable frailty model
        At baseline, fewer than 10% of patients had somatic mutations indicating evolution from antecedent myelodysplastic syndromes (MDSs), which are associated with poor outcome
      2. According to the analysis by Murdock and colleagues, which of the following statements about molecular genetics of CR and measurable residual disease (MRD) associations with baseline characteristics and posttransplant outcomes in older patients with AML is correct?
        In a multivariable model accounting for baseline risk, MRD positivity was significantly associated with LFS
        Patients with sole persisting DNMT3A or TET2 mutations (DT) had posttransplant LFS similar to that of patients who cleared all mutations at remission, whereas patients with other persisting mutations (including in ASXL1) had inferior LFS
        MRD positivity was random and not associated with any pretreatment characteristics of the leukemias
        Posttreatment-emergent mutations always reflect outgrowth of chemoresistant leukemic subclones
      3. According to the analysis by Murdock and colleagues, which of the following statements about clinical implications of factors that drive outcomes of allogeneic HCT for AML in older patients is correct?
        Because older patients with AML are at increased risk of transplant-related toxicity, alternatives to high-intensity conditioning regimens will be necessary to mitigate MRD-associated relapse risk
        Molecular associations with MRD positivity and transplant outcomes in older patients with AML are driven primarily by mutations present in remission
        High baseline molecular risk was driven solely by JAK2 mutations
        In older patients with AML, persistent AML mutations should be eradicated with intensive myeloablative conditioning regimens
       
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